ZCCHC12
protein-codingzinc finger CCHC-type containing 12, the group of Paraneoplastic Ma antigens|Zinc fingers CCHC-type
Gene summary
This gene encodes a downstream effector of bone morphogenetic protein (BMP) signalling. This protein contains a zinc finger domain and functions as a transcriptional coactivator. Variation in this gene may be associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZCCHC12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173798.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 2 | 8 | |||
| missense | 39 | 6 | 1 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 39 | 12 | 3 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_776159.1 | 1 | MANE Select | |
| Ensembl | ENSP00000308921.2 | 1 | MANE Select | |
| RefSeq | NP_001299820.1 | 1 | Standard | |
| Ensembl | ENSP00000609540.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of nuclear beta catenin signaling and target gene transcription
Biological Process
- BMP signaling pathway
- positive regulation of nucleic acid-templated transcription
Molecular Function
- nucleic acid binding
- protein binding
- zinc ion binding
- nuclear receptor transcription coactivator activity
Cellular Component
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000310164
- Coding exons
- 1
- Length
- 3179
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 6
- Defined
- 125740
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.683 | 138 | 162 | 0.849 | 0.0000125 | 2656 |
| Missense (PolyPhen) | 24 | 32.535 | 0.73766 | 678 | ||
| Synonymous | -0.587 | 70 | 64.0 | 1.09 | 0.00000494 | 812 |
| Loss of Function | 1.39 | 3 | 6.97 | 0.431 | 5.98e-7 | 105 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000036 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000024 | 0.000018 | rare |
| South Asian | 0.00016 | 0.000098 | rare |
| Other | 0.00022 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0980
Intolerance Scores
- LoFtool
- 0.356
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 32.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.694
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |